Steroid-resistant sarcoidosis: is antagonism of TNF-α the answer?

2007 ◽  
Vol 112 (5) ◽  
pp. 281-289 ◽  
Author(s):  
Bart G. Denys ◽  
Yves Bogaerts ◽  
Kenneth L. Coenegrachts ◽  
An S. De Vriese
Keyword(s):  
Case Reports ◽  
Controlled Trial ◽  
Critical Role ◽  
Case Series ◽  
Experimental Treatment ◽  
Diagnostic Challenge ◽  
Open Label ◽  
Modest Improvement ◽  
Steroid Resistant ◽  
Tnf Α

Steroid-resistant sarcoidosis has conventionally been treated with various drugs, including methotrexate, azathioprine, cyclophosphamide, cyclosporine, antimalarial drugs and thalidomide, with variable success. There is a compelling need for more efficient and safer alternatives to these agents. Several lines of evidence suggest a critical role of TNF-α (tumour necrosis factor-α) in the initiation and organization of sarcoid granulomas. Inhibition of TNF-α with monoclonal antibodies has therefore received attention as a potential treatment option in therapy-resistant sarcoidosis. A number of case reports and small case series describe successful treatment of refractory disease with infliximab. Preliminary evidence from an RCT (randomized controlled trial) with infliximab in pulmonary sarcoidosis suggests a modest improvement in functional and radiological parameters. In contrast, the results with etanercept have been disappointing, perhaps related to differences in the mechanism of TNF-α blockade. The experience with adalimumab in sarcoidosis is too limited to draw conclusions. An open-label study and an RCT evaluating the efficacy of adalimumab in sarcoidosis with pulmonary and cutaneous involvement respectively, have been initiated. Although TNF-α antagonists appear relatively safe, especially when compared with conventional agents, caution is warranted in view of the increased incidence of tuberculosis, which may be a particular diagnostic challenge in patients with sarcoidosis. Pending publication of the RCTs, the use of TNF-α blockade in sarcoidosis should remain in the realm of experimental treatment.

Valproic Acid in the Management of Delirium

2021 ◽  
pp. 104990912110383
Author(s):  
Carlos Fernandez Cuartas ◽  
Mellar Davis
Keyword(s):  
Valproic Acid ◽  
English Language ◽  
Retrospective Studies ◽  
Case Reports ◽  
Controlled Trial ◽  
Case Series ◽  
Open Label ◽  
Mesh Terms ◽  
Starting Dose ◽  
The Mean

Context: Antipsychotics and benzodiazepines do not improve delirium. Valproic acid (VPA) has been used recently to treat agitation in delirium. Objectives: To review the evidence for VPA in the management of Delirium. Methods: Systematic review. English language, age 19 and above, from 1946 to January 12, 2021. Mesh Terms: “Valproic acid”, “valproate”, “sodium valproate”, “delirium”, “acute mania with delirium” in PubMed and Ovid. Exclusion: Studies of VPA used for diagnoses other than delirium. Results: 21 abstracts were identified and 10 studies were included in the review (252 patients): One prospective open label study (n: 7), 2 case series (n: 22), 4 retrospective studies (n: 219) and 3 case reports (n: 4). No randomized controlled trial (RCT) evaluates the effect of VPA in delirium. 237/250 (94.8%) patients were in the ICU. Mean age was 59.7 (27-87). 153/204 (74%) were male. The mean starting dose was 733 mg/day in 148 patients and the mean dose at follow up was 1061 mg/day in 205 patients. CAM ICU was used to diagnose delirium in 6 reviews. Delirium improved in case series in 19/22 patients. Delirium improved in retrospective studies at day 3 compared to day 1. VPA levels were not consistently reported. Hyperammonemia (12-19%) and thrombocytopenia (9-13%) were the most common side effects. No deaths were attributed to VPA. Conclusion: VPA is being used more frequently for delirium. The evidence is limited to retrospective studies and case series. There is a need for RCT to evaluate the effect of VPA in delirium compared to other alternatives and placebo.

scholarly journals Cardiac Outpouchings: Definitions, Differential Diagnosis, and Therapeutic Approach

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Riccardo Scagliola ◽  
Gian Marco Rosa ◽  
Sara Seitun
Keyword(s):  
Differential Diagnosis ◽  
Clinical Practice ◽  
Therapeutic Approach ◽  
Tissue Characterization ◽  
Case Reports ◽  
Case Series ◽  
Diagnostic Challenge ◽  
Comprehensive Overview ◽  
Search Data ◽  
Data Location

Background and Aims. Cardiac outpouchings encounter a series of distinct congenital or acquired entities (i.e. aneurysms, pseudoaneurysms, diverticula, and herniations), whose knowledge is still poorly widespread in clinical practice. This review aims to provide a comprehensive overview focusing on definition, differential diagnosis, and prognostic outcomes of cardiac outpouchings, as well as further insights on therapeutic options, in order to assist physicians in the most appropriate decision-making. Methods. The material reviewed was obtained by the following search engines: MEDLINE (PubMed), EMBASE, Google Scholar, and Clinical Trials databases, from January 1966 until March 2021. We searched for the following keywords (in title and/or abstract): (“cardiac” OR “heart”) AND (“outpouching” OR “outpouch” OR “aneurysm” OR “pseudoaneurysm” OR “false aneurysm” OR “diverticulum” OR “herniation”). Review articles, original articles, case series, and case reports with literature review were included in our search. Data from patients with congenital or acquired cardiac outpouchings, from prenatal to geriatric age range, were investigated. Results. Out of the 378 papers initially retrieved, 165 duplicates and 84 records in languages other than English were removed. Among the 129 remaining articles, 76 were included in our research material, on the basis of the following inclusion criteria: (a) papers pertaining to the research topic; (b) peer-reviewed articles; (c) using standardized diagnostic criteria; and (d) reporting raw prevalence data. Location, morphologic features, wall motion abnormalities, and tissue characterization were found to have a significant impact in recognition and differential diagnosis of cardiac outpouchings as well as to play a significant role in defining their natural history and prognostic outcomes. Conclusions. Careful recognition of cardiac outpouchings remains a diagnostic challenge in clinical practice. Due to a broad cluster of distinctive and heterogeneous entities, their knowledge and timely recognition play a pivotal role in order to provide the most appropriate clinical management and therapeutic approach.

scholarly journals Probable Neuropsychological & Cognitive Complications due to Cytokine Storm in Patients With COVID-19

2021 ◽  
Vol 0 (0) ◽  
pp. 1-37
Author(s):  
Zahra Keshtgar ◽  
◽  
GH. Reza Chalabianloo ◽  
Niloofar Esmaeili ◽  
◽  
...  
Keyword(s):  
Nervous System ◽  
Case Reports ◽  
Case Series ◽  
Executive Dysfunction ◽  
Inflammatory Factors ◽  
Cytokine Storm ◽  
Case Control Studies ◽  
Necrosis Factor Alpha ◽  
Cross Sectional ◽  
Tnf Α

Introduction: COVID-19 (coronavirus disease 2019) was identified in China in December 2019 for the first time and is rapidly spreading throughout the world as a pandemic. As COVID-19 causes mild to severe acute respiratory syndrome, most studies in this context have focused on pathogenesis primarily in the respiratory system. However, evidence shows that the central nervous system (CNS) may also be affected by COVID-19. Since COVID-19 is spreading, it is imperative to study its possible cognitive effects in patients suffering and recovering from COVID-19. Methods: The articles used in this study were searched by keywords such as Cytokine storm and covid-19, covid-19 and executive dysfunction, cognitive disorder and covid-19, CNS and covid 19, Coronavirus, Neuroinvasion in science direct, Scopus, PubMed, Embase, and Web of Science databases based on Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. The study will assess all observational studies published between December 2019 and April 2021 in peer-reviewed journals, including cross-sectional, cohort, case-control studies, case reports and case series. The search result was 106 articles, of which 73 articles related to Covid-19, the stages of infection by this virus, its effect on the nervous system and neurological symptoms, the cytokine storm caused by this infection, and the possible cognitive consequences caused by this virus in patients, has been reviewed. Other articles were not checked due to their limited relevance to the topic under discussion. Results: Studies show that neurons may be directly affected by SARS-CoV-1 and SARS-CoV-2. Furthermore, various studies indicate that systemic inflammation (so-called "cytokine storm") is also responsible for brain damage induced by infection with SARS-CoV-1 and SARS-CoV-2. Such a way that this patients showed elevated levels of interleukin (IL-), 6, 8, and 10 and of tumor necrosis factor-alpha (TNF- α) in their blood. Conclusion: Various cognitive defects following an increase level of cytokines such as TNF-α and IL-6,8 have been observed. Therefore, due to the increase level of these pro-inflammatory factors in the brains of these patients, cognitive deficits can be expected, which need further investigation.

scholarly journals Antidopaminergic treatment is associated with reduced chorea and irritability but impaired cognition in Huntington’s disease (Enroll-HD)

2020 ◽  
Vol 91 (6) ◽  
pp. 622-630
Author(s):  
Kate L Harris ◽  
Wei-Li Kuan ◽  
Sarah L Mason ◽  
Roger A Barker
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Case Reports ◽  
Controlled Trial ◽  
Rate Of Change ◽  
Control Group ◽  
Open Label ◽  
Double Blind ◽  
Before And After ◽  
Rate Of Decline

ObjectivesAlterations in dopamine neurotransmission underlie some of the clinical features of Huntington’s disease (HD) and as such are a target for therapeutic intervention, especially for the treatment of chorea and some behavioural problems. However, justification for such an intervention is mainly based on case reports and small open label studies and the effects these drugs have on cognition in HD remain unclear.MethodsIn this study, we used the Enroll-HD observational database to assess the effects of antidopaminergic medication on motor, psychiatric and cognitive decline, over a 3-year period. We first looked at the annual rate of decline of a group of HD patients taking antidopaminergic medication (n=466) compared with an untreated matched group (n=466). The groups were matched on specified clinical variables using propensity score matching. Next, we studied a separate group of HD patients who were prescribed such medications part way through the study (n=90) and compared their rate of change before and after the drugs were introduced and compared this to a matched control group.ResultsWe found that HD patients taking antidopaminergic medication had a slower progression in chorea and irritability compared with those not taking such medications. However, this same group of patients also displayed significantly greater rate of decline in a range of cognitive tasks.ConclusionIn conclusion we found that antidopaminergic treatment is associated with improvements in the choreic movements and irritability of HD but worsens cognition. However, further research is required to prospectively investigate this and whether these are causally linked, ideally in a double-blind placebo-controlled trial.

scholarly journals Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Daria Piacentino ◽  
Annalisa Maraone ◽  
Valentina Roselli ◽  
Isabella Berardelli ◽  
Massimo Biondi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ethical Issues ◽  
Case Reports ◽  
Treatment Strategies ◽  
Case Series ◽  
Symptom Improvement ◽  
Open Label ◽  
Cross Sectional ◽  
Positive Effects ◽  
Nicotine Administration

Abstract Background Preliminary studies have tested nicotine as a novel treatment for OCD patients who respond partially/incompletely or not at all to first and second-line treatment strategies, with the former represented by SSRIs or clomipramine, and the latter by switching to another SSRI, or augmentation with atypical antipsychotics, and/or combination with/switching to cognitive–behavioural therapy. Some studies found nicotine-induced reduction of obsessive thoughts and/or compulsive behaviour in OCD patients. We aimed to evaluate the efficacy of nicotine administration in OCD patients. Methods We searched the PubMed, ScienceDirect Scopus, CINHAL, Cochrane, PsycINFO/PsycARTICLES, and EMBASE databases from inception to the present for relevant papers. The ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ (PRISMA) standards were used. We included all studies focusing on the effects of nicotine administration on OCD patients’ obsessions or compulsions. Studies could be open-label, cross-sectional, randomized controlled trials, case series or case reports. Results A total of five studies could be included. Nicotine administration may ameliorate behavioural features and recurrent thoughts of severe, treatment-resistant OCD patients; however, in one study it was not associated with OC symptom improvement or cognitive enhancement across various executive function subdomains. Conclusions Although encouraging, the initial positive response from the use of nicotine in OCD needs testing in large controlled studies. This, however, raises ethical issues related to nicotine administration, due to its addiction potential, which were not addressed in the limited literature we examined. As an alternative, novel treatments with drugs able to mimic only the positive effects of nicotine could be implemented.

scholarly journals Rosiglitazone Decreases Serum Bone-Specific Alkaline Phosphatase Activity in Postmenopausal Diabetic Women

2007 ◽  
Vol 92 (9) ◽  
pp. 3523-3530 ◽  
Author(s):  
Zehra Berberoglu ◽  
Alptekin Gursoy ◽  
Nilufer Bayraktar ◽  
Ayse Canan Yazici ◽  
Neslihan Bascil Tutuncu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Controlled Trial ◽  
Lifestyle Changes ◽  
Control Group ◽  
Long Term Effects ◽  
Open Label ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Rosiglitazone Treatment

Abstract Objectives: Our objectives were to evaluate the effect of rosiglitazone on bone metabolism and to assess the association between changes in bone turnover parameters and plasma cytokine levels in postmenopausal diabetic women. Design: This was a 12-wk open-label randomized-controlled trial. Patients or Other Participants: A total of 56 obese postmenopausal women with newly diagnosed diabetes and 26 nondiabetic healthy controls matched for age and body mass index were included in the study. Interventions: The subjects were instructed to follow a weight-maintenance diet. Half were randomly assigned to receive rosiglitazone 4 mg/d, and the other half remained on diet alone. Main Outcome Measures: Before and after the interventions, metabolic bone markers and serum cytokine levels were assessed. Results: Serum total alkaline phosphatase (ALP) and bone-specific ALP levels were statistically significantly lower 12 wk after initiation of rosiglitazone treatment. There were no statistically significant changes in osteocalcin levels among the three groups or in deoxypyridinoline levels in the rosiglitazone group. At the end of 12 wk, all patients had statistically significantly decreased IL-1β and TNF-α levels compared with baseline. Changes in bone-specific ALP levels showed a moderate negative correlation with the changes in the TNF-α levels after rosiglitazone treatment and after diet in the diabetic control group. Conclusions: Rosiglitazone use is associated with reduced bone formation at earlier stages in postmenopausal diabetic women. The cytokine-lowering effects of rosiglitazone and lifestyle changes could reverse the early inhibitory effect of rosiglitazone therapy on bone formation. Further studies will clarify the long-term effects of rosiglitazone therapy on bone loss and fracture.

scholarly journals P416 Results of the first paediatric randomised controlled trial of faecal microbiota transplant for ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S379-S380
Author(s):  
N Pai ◽  
J Popov ◽  
L Hill ◽  
E Hartung ◽  
K Grzywacz ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Healthy Donor ◽  
Activity Index ◽  
Case Reports ◽  
Case Series ◽  
Faecal Microbiota ◽  
Open Label ◽  
Randomised Controlled

Abstract Background The role of faecal microbiota transplant (FMT) for the treatment of ulcerative colitis (UC) has been reported across 4 randomised-controlled trials (RCT) in adults. Promising data have emerged from small, open-label paediatric case series and case reports but a proper blinded, placebo-controlled RCT has not been described in children. We report results from the first multicentre RCT of FMT in paediatric UC patients, conducted over 36 months in Ontario and Quebec, Canada. Methods We enrolled 25 children, ages 4–17 years old with active UC across two tertiary IBD clinics. Patients had active inflammation and remained on stable doses of medication at entry. Blinded participants received enemas containing healthy donor stool (active) or normal saline (placebo), 2×/week for 6 weeks. Faecal calprotectin (fCal), C-reactive protein (CRP), and paediatric ulcerative colitis activity index (PUCAI) scores were compared between groups during intervention, and at four follow-up time points over 30 weeks. Donor and recipient stools were measured for 16s rRNA and metagenomics analyses. Results In intention-to-treat (ITT) analysis, FMT (n = 13) at 6 weeks was more likely to improve clinical response (OR 9.3, 95% CI [0.7, 122.6]), CRP (OR 4.7, 95% CI [0.8, 28.4]), and fCal (OR 13.3, 95% CI [1.1, 166.4]) from baseline compared with placebo (n = 12). FMT at 30 weeks was also more likely than placebo to improve clinical response, CRP, and fCal (Table 1). In ITT analysis of the open-label arm (n = 7), FMT at 6 weeks and 30 weeks decreased CRP (−42.9%, −28.6%), fCal (−28.6%, −42.9%), and PUCAI score (−14.3%, −42.9%) from baseline. Conclusion Serial FMT enemas containing healthy donor microbiota led to greater improvements in serum and stool inflammatory markers, and rates of clinical response, in paediatric patients with active UC compared with placebo. These improvements largely persisted beyond 6 months after final FMT treatment. This study offers the strongest preliminary evidence, from a blinded, placebo-controlled multicentre RCT for the role of FMT in the management of paediatric UC.

scholarly journals Apremilast as an Off-Label Therapeutic Agent

2021 ◽  
Vol 5 (3) ◽  
pp. 203-227
Author(s):  
Justin Marson ◽  
Mark Lebwohl
Keyword(s):  
Atopic Dermatitis ◽  
Psoriatic Arthritis ◽  
Combination Therapy ◽  
Hidradenitis Suppurativa ◽  
Case Reports ◽  
Case Series ◽  
Open Label ◽  
Off Label ◽  
Inflammatory Dermatoses ◽  
Randomized Control

Objective: To review the literature regarding the efficacy and safety of off-label use of apremilast in combination therapies for psoriasis and psoriatic arthritis and for other currently off-label inflammatory dermatoses. Methods: The Medline database was queried for all relevant articles published between 2014 and 2021 using exploded MeSH terms and keywords pertaining to the following themes: off-label, combination therapy, biologics, biologic therapy, methotrexate, and systemic psoriasis therapy. The Boolean term “AND” was used to find the intersection of these themes with the term “apremilast.” Results: 8 case series and 6 case reports investigated the use of apremilast in combination therapy for psoriasis and psoriatic arthritis. Addition of apremilast improved PASI scores by 31.8-77.4% among case series and 80-100% among case reports with adverse effects primarily consisting of gastrointestinal symptoms. 5 randomized-control trials (RCT), 9 open-label trials, 18 case series, and 30 case reports investigated the use of apremilast for off-label dermatoses. In RCTs, apremilast showed potential efficacy for atopic dermatitis and hidradenitis suppurativa. Open-label trials found apremilast efficacious for atopic dermatitis, allergic contact dermatitis, chronic pruritus, cutaneous sarcoidosis, discoid lupus erythematosus, hidradenitis suppurativa, lichen planus, prurigo nodularis, rosacea, and vitiligo. Limitations: Small sample size and short follow duration up for available randomized-control and open-label trials. Current data from case series/reports potentially limits generalizability of findings. Conclusion: Apremilast's safety profile makes it a potential efficacious, non-biologic systemic agent for monotherapy and combination therapy for a wide range of inflammatory dermatoses.

The Use of Janus Kinase Inhibitors in Vitiligo: A Review of the Literature

2019 ◽  
Vol 23 (3) ◽  
pp. 298-306 ◽  
Author(s):  
Nicole Relke ◽  
Melinda Gooderham
Keyword(s):  
Kinase Inhibitors ◽  
Case Reports ◽  
Normal Skin ◽  
Unmet Need ◽  
Case Series ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Open Label ◽  
Attractive Therapeutic Target ◽  
Favorable Safety

Vitiligo is a common acquired depigmenting disorder characterized by the development of white macules and patches due to the loss of melanocytes. Patients with vitiligo can be stigmatized by society, making the disease a source of psychological stress that can considerably affect quality of life. The goal of vitiligo treatment is to obtain skin repigmentation in the majority of cases, and less commonly to depigment the remaining normal skin. There is no consistent, long-term, durable therapy for vitiligo for all patients, highlighting the unmet need for new safe and effective therapies to control this disease. Recently, JAK inhibitors have been explored as a promising novel treatment option in vitiligo. The JAK and signal transducers and activators of transcription (STAT) pathway is an attractive therapeutic target because IFN-γ–dependent cytokines produced through this pathway have been implicated in the pathogenesis of disease. This literature review describes vitiligo pathophysiology, explains the usefulness of the JAK inhibitors for treatment, and summarizes published case reports, case series, and open-label studies. Research outlined here shows JAK inhibitors in patients with vitiligo have a favorable safety profile and effectively produce repigmentation of lesions, especially with concomitant ultraviolet exposure. Additional studies are required to confirm efficacy, establish safety, and investigate durability of repigmentation.

scholarly journals Congenital, Intrapartum and Postnatal Maternal-Fetal-Neonatal SARS-CoV-2 Infections: A Narrative Review

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3570
Author(s):  
Rafael A. Caparros-Gonzalez ◽  
María Angeles Pérez-Morente ◽  
Cesar Hueso-Montoro ◽  
María Adelaida Álvarez-Serrano ◽  
Alejandro de la Torre-Luque
Keyword(s):  
Amniotic Fluid ◽  
Pregnant Women ◽  
Umbilical Cord ◽  
Case Reports ◽  
Controlled Trial ◽  
Case Series ◽  
Narrative Review ◽  
Before And After ◽  
Positive Results ◽  
Cervical Secretion

Background: There is inconclusive evidence regarding congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. A narrative review was conducted with the aim of guiding clinicians on the management of pregnant women with respect to congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections and breastfeeding during the COVID-19 pandemic. Methods: Searches were conducted in Web of Science, PubMed, Scopus, Dialnet, CUIDEN, Scielo, and Virtual Health Library to identify observational, case series, case reports, and randomized controlled trial studies assessing the transmission of SARS-CoV-2 from mother to baby and/or through breastfeeding during the COVID-19 pandemic. Results: A total of 49 studies was included in this review, comprising 329 pregnant women and 331 neonates (two pregnant women delivered twins). The studies were performed in China (n = 26), USA (n = 7), Italy (n = 3), Iran (n = 2), Switzerland (n = 1), Spain (n = 1), Turkey (n = 1), Australia (n = 1), India (n = 1), Germany (n = 1), France (n = 1), Canada (n = 1), Honduras (n = 1), Brazil (n = 1), and Peru (n = 1). Samples from amniotic fluid, umbilical cord blood, placenta, cervical secretion, and breastmilk were collected and analyzed. A total of 15 placental swabs gave positive results for SARS-CoV-2 ribonucleic acid (RNA) on the fetal side of the placenta. SARS-CoV-2 RNA was found in seven breastmilk samples. One umbilical cord sample was positive for SARS-CoV-2. One amniotic fluid sample tested positive for SARS-CoV-2. Conclusions: This study presents some evidence to support the potential of congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. Mothers should follow recommendations including wearing a facemask and hand washing before and after breastfeeding.

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